STUDY OF CARDIAC ARRHYTHMIAS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal of this project is the study of mechanisms of cardiac arrhythmias with complex cardiac cell model connected in multicellular tissue. The origin of cardiac arrhythmia can be long QT syndrome, dysfunction of Ca2+ handling, or reduced conductivity of heart tissue. The cardiac arrhythmia can lead to ventricular fibrillation and sudden cardiac death. Recently we developed a model of action potential for mouse cardiac ventricular myocyte that includes 15 ionic currents and transporters and advanced Ca2+ handling system with the help of the Grant from PSC (MCB010020P). The model reproduced voltage-clamp experiments on major ionic currents, Ca2+ fluxes responsible for the myocyte contraction, and action potential. This model will be used in this project for simulation of action potential generation and propagation in multicellular cardiac tissue. Methods of nonlinear dynamics and chaos theory will be used to elucidate mechanisms of arrhythmia generation because of genetic mutations in ion channels responsible for IKto, IKur, or intercellular connections (Connexin43).